VULNERABILITY OF ISLETS IN THE IMMEDIATE POSTTRANSPLANTATION PERIOD -DYNAMIC CHANGES IN STRUCTURE AND FUNCTION

To learn more about islet vulnerability in the immediate posttransplan t period, 400 syngeneic islets were transplanted under the kidney caps ule of B6AF1 mice, Three groups of recipients were used: normal mice ( normal), streptozotocin (STZ)-diabetic (diabetic), and STZ-diabetic ke pt hypo- or normoglycemic with insulin pellets (diabetic-normalized). Normoglycemia was achieved in all three groups 14 days after transplan tation; however, in the diabetic and diabetic-normalized groups, blood glucose levels throughout the posttransplantation period were respect ively higher and lower than in the normal group, Grafts were harvested 1, 3, 7, and 14 days after transplantation and analyzed for morpholog y, beta-cell death, beta-cell mass, insulin content, and insulin mRNA expression, In all groups, substantial damage in islet grafts was foun d on days 1 and 3 with apoptotic nuclei and necrotic cores; on day 3, beta-cell death was significantly higher in the diabetic group than in the other groups, Tissue remodeling occurred in all groups with stabl e graft appearance on day 14; the actual beta-cell mass of the grafts was lowest in the diabetic group, Graft insulin content decreased in a ll groups on day 1 and feb even further on days 3 and 7. Insulin mRNA levels of grafts retrieved from both the diabetic and diabetic-normali zed group were lower than those from the normal group already by day 1 and remained lower on day 14, In conclusion, the first few days of is let transplantation, even under the most advantageous circumstances of excellent metabolic control, are characterized by dynamic changes, wi th substantial islet cell dysfunction and death followed by tissue rem odeling and then stable engraftment.